Elise Donovan,1,2 Anne Jaquiery,1,2,3 Mark Oliver,1,2 Serina Hancock1 and Frank Bloomfield1,2,3
1 Liggins Institute, , Auckland; 2 Gravida: National Centre for Growth and Development, NZ; 3 Department of Paediatrics, Child and Youth Health, , Auckland
Sheep conceived and carried as twins, and twins reduced to a singleton pregnancy (reductions) in early gestation, have altered growth trajectories, greater fat mass and less lean mass in adulthood than those conceived as singletons. Adult males conceived as twins are also less insulin sensitive than singletons, with reductions intermediate. We hypothesized that adipose tissue from twins and reductions would exhibit an inflamed and insulin resistant phenotype compared with singletons. Twin pregnancies in sheep were randomised to reduction of one twin on day 42 of a 148 d pregnancy. At 2 yr of age, offspring omental, perirenal, and subcutaneous adipose tissue were collected. GLUT4, GLUT1, IL6, and TNFa mRNA expression were measured with quantitative PCR. Data are presented as fold difference with 99% confidence intervals. In male omental adipose, twins and reductions both had significantly greater expression of GLUT4 (1.41 (1.23-1.62) and 1.74 (1.74-1.74)) and GLUT1 (1.22 [1.18-1.26] and 2.38 [2.17-2.60]) compared to singletons, and IL6 was significantly greater in reductions compared to singletons (1.54 [1.38-1.71]). In male perirenal adipose TNFa was significantly greater in reductions compared to singletons (1.62 [1.21-2.16]), but IL6 was significantly lower in reductions and twins compared to singletons (0.58 [0.42-0.80] and 0.46 [0.33-0.63]). In male subcutaneous adipose TNFa (0.65 (0.55-0.75) and 0.66 (0.56-0.76) and IL6 (0.36 (0.23-0.59), and 0.32 (0.18-0.56) were significantly lower in reductions and twins compared to singletons. In female omental adipose, TNF expression was significantly greater in reductions than in singletons (1.30 [1.23-1.39]). IL6, however, was significantly greater in twins compared to both singletons and reductions (1.48 [1.30-1.68] and 1.31 [1.12-1.52]). No major effects were observed in female perirenal or subcutaneous adipose. Being conceived as a twin, regardless of whether the twin pregnancy is carried to term, alters adult adipose inflammatory and glucose transporter phenotype in a sexually dimorphic manner.